Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3

Hatami N, Büttner C, Bock F, Simfors S, Musial G, Reis A, Cursiefen C, Clahsen T (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Communications Biology Nature Research

Book Volume: 5

Article Number: 950

Journal Issue: 1

DOI: 10.1038/s42003-022-03923-7

Abstract

Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection. Endogenous regulation of lymphangiogenesis is only partly understood. Here we use the normally avascular cornea as a model to identify endogenous regulators of lymphangiogenesis. Quantitative trait locus analysis of a large low-lymphangiogenic BALB/cN x high-lymphangiogenic C57BL/6 N intercross and prioritization by whole-transcriptome sequencing identify a novel gene responsible for differences in lymphatic vessel architecture on chromosome 17, the cystathionine β-synthase (Cbs). Inhibition of CBS in lymphatic endothelial cells results in reduce proliferation, migration, altered tube-formation, and decrease expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGF-R2) and VEGF-R3, but not their ligands VEGF-C and VEGF-D. Also in vivo inflammation-induced lymphangiogenesis is significantly reduce in C57BL/6 N mice after pharmacological inhibition of CBS. The results confirm CBS as a novel endogenous regulator of lymphangiogenesis acting via VEGF receptor 2 and 3-regulation and open new treatment avenues in diseases associated with pathologic lymphangiogenesis.

Authors with CRIS profile

Christian Büttner Lehrstuhl für Humangenetik André Wiesmann da Silva Reis Lehrstuhl für Humangenetik

Involved external institutions

Universität zu Köln DE Germany (DE)

How to cite

APA:

Hatami, N., Büttner, C., Bock, F., Simfors, S., Musial, G., Reis, A.,... Clahsen, T. (2022). Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3. Communications Biology, 5(1). https://dx.doi.org/10.1038/s42003-022-03923-7

MLA:

Hatami, Niloofar, et al. "Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3." Communications Biology 5.1 (2022).

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